{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T10:16:43Z","timestamp":1771928203983,"version":"3.50.1"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ulcerative colitis (UC) is subtype of inflammatory bowel disease that is frequently comorbid with anxiety disorders. However, effective dual-targeting therapies are still lacking. Hyperoside (HYP), a natural flavonoid, exhibits anti-inflammatory and neuroprotective properties, yet its potential therapeutic effects on UC and associated anxiety, as well as the underlying mechanisms, remain largely unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A murine model of DSS-induced colitis was established and treated with HYP. Disease activity was assessed through body weight, colon length, and histopathology. Anxiety-like behaviors were evaluated using open field and elevated plus maze tests. Neuroinflammation was examined through immunohistochemistry of BDNF expression and microglial activation. Gut microbiota composition was profiled by metagenomic sequencing, and metabolomic profiling was conducted using the Q300 Kit. Network pharmacology and molecular docking were employed to predict signaling pathways, which were further validated by Western blotting. Additionally, antibiotic depletion experiments were conducted to determine microbiota dependency.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HYP administration significantly ameliorated DSS-induced colitis, as evidenced by attenuated weight loss, restored colon length, and improved histopathology. It suppressed pro-inflammatory cytokines (TNF-\u03b1, IL-6, IL-1\u03b2) and restored intestinal barrier integrity by upregulating Mucin-2 and ZO-1. Furthermore, HYP also alleviated anxiety-like behaviors and mitigated neuroinflammation by increasing BDNF levels and suppressing microglial activation. HYP treatment also restored gut microbial homeostasis, enriching beneficial bacteria such as\n                      <jats:italic>Enterobacter ludwigii<\/jats:italic>\n                      while reducing the abundance of\n                      <jats:italic>Enterobacter hormaechei, Escherichia coli<\/jats:italic>\n                      , and\n                      <jats:italic>Acinetobacter baumannii<\/jats:italic>\n                      . Metabolomic analysis revealed that HYP significantly promoted arginine biosynthesis. Network pharmacology and molecular docking identified the MAPK, PI3K-Akt, and NF-\u03baB pathways as potential targets, with HYP showing strong binding affinity to MAPK3, AKT1, and NF\u03baB1. Importantly, the therapeutic effects of HYP were abolished in microbiota-depleted mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings demonstrate that HYP effectively alleviates DSS-induced colitis and comorbid anxiety-like behaviors. Its efficacy is dependent on the gut microbiota and is associated with the restoration of microbial homeostasis, enhancement of arginine metabolism, and modulation of the MAPK\/PI3K-Akt\/NF-\u03baB signaling pathways. HYP represents a promising microbiota-targeting therapeutic candidate for UC and its neuropsychiatric comorbidities.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1734356","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T06:41:15Z","timestamp":1769668875000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Microbiota-driven therapeutic efficacy of Hyperoside in ulcerative colitis and associated anxiety"],"prefix":"10.3389","volume":"16","author":[{"given":"Li","family":"Yin","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Xu","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Shandong University of Traditional Chinese Medicine","place":["Jinan, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-nan","family":"Shan","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Hubei University of Chinese Medicine","place":["Wuhan, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhilin","family":"He","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Shandong University of Traditional Chinese Medicine","place":["Jinan, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanbin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Institute of Neuroimmunology, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine","place":["Jinan, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s12974-021-02368-9","article-title":"Social isolation induces neuroinflammation and microglia overactivation, while dihydromyricetin prevents and improves them","volume":"19","author":"Al Omran","year":"2022","journal-title":"J. neuroinflammation"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1177\/0148607115581374","article-title":"Pretreatment and treatment with L-arginine attenuate weight loss and bacterial translocation in dextran sulfate sodium colitis","volume":"40","author":"Andrade","year":"2016","journal-title":"JPEN J. parenteral enteral Nutr."},{"key":"B3","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/S2468-1253(21)00014-5","article-title":"Prevalence of symptoms of anxiety and depression in patients with inflammatory bowel disease: a systematic review and meta-analysis","volume":"6","author":"Barberio","year":"2021","journal-title":"Lancet Gastroenterol. hepatol"},{"key":"B4","first-page":"13","article-title":"BDNF attenuates IL-1\u03b2-induced F-actin remodeling by inhibiting NF-\u03baB signaling in hippocampal neurons","volume":"35","author":"Cai","year":"2014","journal-title":"Neuro Endocrinol. letters"},{"key":"B5","doi-asserted-by":"publisher","first-page":"8161","DOI":"10.1111\/jcmm.14686","article-title":"Taraxacum officinale extract ameliorates dextran sodium sulphate-induced colitis by regulating fatty acid degradation and microbial dysbiosis","volume":"23","author":"Chen","year":"2019","journal-title":"J. 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